Ardisiatetrons A and B: tetronic acid derivatives and triterpenes from the leaves of Ardisia quinquegona and their biological activity.

From the leaves of Ardisia quinquegona, two alkylated tetronic acid derivatives, named ardisiatetrons A and B (1, 2), and four triterpenoids (3-6) were isolated together with one known compound (7) by a combination of various kinds of chromatography. The structure of new methyl migrated triterpene (3) was confirmed by X-ray crystallographic analysis. Compounds 2, 3, and 7 showed moderate anti-Leishmania activity and cytotoxicity towards A549 cells.

Microtropins Q-W, ent-Labdane Glucosides: Microtropiosides G-I, Ursane-Type Triterpene Diglucoside and Flavonol Glycoside from the Leaves of Microtropis japonica.

Microtropins Q-W, (2S,3R)-2-ethyl-2,3-dihydroxybutyrate of various glucosides and glucose, as well as three ent-labdane diterpenoid glucosides, named microtropiosides G, H and I, an ursane-type triterpene diglucoside and a flavonoid glycoside were isolated from the MeOH extract of the leaves of Microtropis japonica. The structure of microtropioside A, also isolated from the branches of M. japonica, was elucidated spectroscopically in a previous experiment and was found to possess a rare seven-membered oxyrane ring. Its structure was confirmed by X-ray crystallographic analysis of its pentaacetate.

The Influence of Neoadjuvant Chemotherapy with Docetaxel, Nedaplatin and 5-Fluorouracil After Esophagectomy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) with docetaxel, nedaplatin and 5-fluorouracil (5-FU) in esophageal cancer may adversely affect the postoperative clinical course following esophagectomy. PATIENTS AND METHODS: We investigated the perioperative white blood cell count (WBC), C-reactive protein (CRP), serum albumin, body temperature (BT), heart rate (HR), respiratory rate (RR), water balance, partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio, postoperative complications and systemic inflammatory response syndrome (SIRS) in patients who underwent NAC or surgery alone (SA group). RESULTS: In the NAC group, the preoperative WBC (p=0.015) and postoperative day (POD) 3 BT (p=0.049), as well as RR (p=0.037) were lower, whereas the POD 2 PaO2/FiO2 ratio was higher (p=0.047), compared to the SA group. No differences in the incidence of postoperative complications and SIRS were observed between the groups. CONCLUSION: NAC using docetaxel, nedaplatin and 5-fluorouracil was tolerated and feasible in esophageal cancer.

Impact of Branched-Chain Amino Acid-Enriched Nutrient on liver Cirrhosis with Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization in Barcelona Clinic Liver Cancer Stage B: A Prospective Study.

BACKGROUND: In decompensated liver cirrhosis, hypoalbuminemia still persists even after they have been treated with branched-chain amino acid (BCAA) granules. We prospectively evaluated whether BCAA enriched nutrient switched from BCAA granules would increase the serum albumin level, and consequently extend the survival time after hepatocellular carcinoma (HCC) treatment. METHODS: This study included 77 patients treated for liver cirrhosis with HCC. After the nutritional assessment, all patients initially received BCAA granules. In patients with unchanged or decreased serum albumin levels, BCAA granules were discontinued and BCAA enriched nutrient was started. Transcatheter arterial chemembolization (TACE) for HCC were performed in those with an improved Child-Pugh score. RESULTS: TACE were performed following the aggressive intervention with BCAA nutritional education in 54 of 77 (70.1%) patients. Finally, survival time was significantly extended in the TACE group (P<0.0001). CONCLUSION: Timely aggressive nutritional intervention in Barcelona Clinic Liver Cancer stage B HCC, namely, early partial replacement with BCAA enriched nutrient may consequently improve the treatment outcome of HCC.

[A case of a recurrent hepatic metastasis occurred after curative resection of ascending colon cancer and a hepatic metastasis responding completely to capecitabine plus bevacizumab].

Although hepatic resection is the most effective therapy for patients with liver metastasis from colorectal carcinoma, a subset of patients cannot undergo surgical treatment for several reasons, including age-related general health decline or poor conditions associated with coexisting diseases, even if the lesions are resectable. A 75-year-old man with a recurrent lesion in the liver underwent right hemicolectomy and partial hepatic resection to treat colonic cancer and a liver metastasis, followed by uracil and tegafur plus Leucovorin( UFT+LV) as adjuvant chemotherapy at 6 months after the initial surgery. Although the lesion was resectable, the patient preferred chemotherapy to surgery, and capecitabine plus oxaliplatin plus bevacizumab was administered; however, the treatment was stopped in the middle of the second course because of oxaliplatin -related toxicities. Capecitabine plus bevacizumab was introduced as the following chemotherapy regimen, and no adverse reactions were observed during this therapy. After 5 courses of administration, the lesion disappeared on CT examination, and no new lesions were found after 9 courses. Thus, the treatment response was classified as complete response (CR) and remains as such after 13 courses.

Three new aliphatic glycosides from the leaves of Antidesma japonicum Sieb. et Zucc.

From the 1-BuOH-soluble fraction of an MeOH extract of leaves of Antidesma japonicum, three new aliphatic glycosides, α-L-arabinofuranosyl-(1 → 6)-ß-D-glucopyranosides of (6R,9R)-megastigma-4,7-dien-9-ol-3-one, (Z)-hex-3-en-1-ol, and methyl 2-hydroxy-2-(1'-hydroxyethyl)pentanoate 1'-O-ß-D-glucopyranoside, were isolated, along with seven known compounds.

Linderolides A-F, eudesmane-type sesquiterpene lactones and linderoline, a germacrane-type sesquiterpene from the roots of Lindera strychnifolia and their inhibitory activity on NO production in RAW 264.7 cells in vitro.

From the roots of Lindera strychnifolia, seven sesquiterpenes, named linderolides A-F and linderoline, were isolated together with six known compounds. The structures of linderolides A-F were elucidated to be eudesmane-type sesquiterpenes and linderoline was found to be a derivative of a germacrane-type sesquiterpene. Their structures were elucidated by means of spectroscopic evidence and that of linderolide A was confirmed by X-ray analysis. The inhibitory activity toward NO production was assayed using RAW264.7 cells with evaluating the cell growth by MTT method, linderolides C, D and F being found to be moderately active.

The quaternary indole alkaloids from two Sumatran Lerchea species.

The Sumatran forest plants Lerchea cf. bracteata and L. parviflora were found to contain alkaloids and their extract showed siginificant activity toward some testing pathogenic microbes. Isolation work on L.cf bracteata yielded known quaternary alkaloid N(b)-methylantirhine (2) while L. parviflora gave 5,6-dihydroflavopereirine (3).

A case of esophageal cancer with multiple lymph node metastases which responded to neoadjuvant chemotherapy (DCF therapy).

It is difficult to perform radical surgery for esophageal cancer with multiple lymph node metastases. Therefore, effective neoadjuvant adjuvant treatment is necessary to achieve successful radical resection. The use of neoadjuvant chemotherapy of docetaxel, cisplatin (CDOP) and 5-fluorouracil (5-FU) (DCF) in an advanced case is reported. The patient (a 67-year-old female) was diagnosed with esophageal cancer, T3, N4, M0, stage IVa with a large number of lymph node metastases in the mediastinum and in the abdominal cavity. Neoadjuvant DCF chemotherapy was initiated in August 2006. Adverse events were mild. A complete response of the lymph node metastases in the abdominal cavity and a partial response of the esophageal lesion were achieved. The surgical procedure included a right thoracolaparotomy followed by a subtotal excision of the esophagus and two-field lymph node dissection. The cancer was diagnosed to be moderately differentiated squamous cell cancer, pT2, pN4(3c) and pstage IVa. The histological efficacy of the chemotherapy was determined to be grade 1a. Two additional courses of DCF therapy were administered followed by postoperative adjuvant chemotherapy.

Chemical constituents of imported Rosae fructus.

Rosae fructus is a traditional Chinese crude drug, used for purgative purposes. It is included in the Japanese Pharmacopoeia XV, in which its origin is stated to be Rosa multiflora Thunberg. These days, some imported Rosae fructus are on the market and the pharmacological activity of the imported product is in question. The chemical constituents of Japanese Pharmacopoeial Rosae fructus, imported from the People's Republic of China and whose plant origin is expected to be Rosa aff. multiflora, were investigated to give 2-hydroxynaringin 5-O-beta-D-glucopyranoside and L(S)-pyroglutaminic acid derivative as new compounds. However, although we made every effort, the major flavonoids in R. multiflora, multiflorins A and B, and multinoside A acetate, could not be isolated.

Secondary metabolites of Cinnamosma madagascariensis and their alpha-glucosidase inhibitory properties.

Two new drimane-type sesquiterpenes, cinnamadin (1) and cinnamodial 11alpha,12beta-dimethyl acetal (2), together with pereniporin B (3), ugandensolide (4), polygodial (5), capsicodendrin, cinnamodial (6), sitosterol, stigmasterol, lignoceric acid, cinnamosmolide (7), D-mannitol, and delta-tocotrienol were isolated from Cinnamosma madagascariensis. The structures of the new compounds were determined by physical, chemical, and spectroscopic evidence. Compound 7 and D-mannitol were isolated in high yield (5% and 1.36%, respectively). Evaluation of the alpha-glucosidase inhibitory properties of the isolated metabolites demonstrated that compounds 1 and 4 show moderate effects, while cinnamodial (6) exhibited the most potent activity. The chemosystematics of Cinnamosma species are also discussed.

Synergistic effects of multiple treatments, and both DNA and RNA direct bindings on, green tea catechins.

This article reviews two main topics: (1) the synergistic effects of multiple treatments with green tea catechin and (2) the direct binding of (-)-epigallocatechin gallate (EGCG) to both DNA and RNA molecules. Japanese drink green tea throughout the day, so we studied whether multiple treatments of cells with EGCG would enhance the expression of apoptosis-related genes, such as growth arrest and DNA damage-inducible gene (GADD153) and cyclin-dependent kinase inhibitor gene (p21(waf1)): The results suggest that the synergistic enhancement of both GADD153 and p21(waf1) gene expressions by multiple treatments plays a significant role in human cancer prevention with green tea beverage. Our previous observation-that nucleic acids extracted from catechin-treated cells are colored-allowed us to speculate that catechins directly interact with nucleic acids. Surface plasmon resonance assay (Biacore) indicated that four catechins, EGCG, (-)-epicatechin gallate (ECG), (+)-gallocatechin gallate (GCG), and (+)-catechin gallate (CG), bound to DNA oligomers. Cold spray ionization mass spectrometry (CSI-MS) analysis showed that one to three EGCG molecules bound to single-stranded 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to double-stranded AG:CT oligomers of various nucleotide lengths. Double-stranded DNA (dsDNA) oligomers were detected only as EGCG-bound forms at high temperature, whereas at low temperature both the free and bound forms were detected, suggesting that EGCG protects double-stranded DNA oligomers from double-stranded melting into single-stranded DNA. We assume that catechins accumulate in both double-stranded DNA and RNA molecules through multiple administrations of green tea beverage in in vivo, and that the accumulated green tea catechins play a significant role for human cancer prevention.

DNA and RNA as new binding targets of green tea catechins.

The significance of catechins, the main constituent of green tea, is being increasingly recognized with regard to cancer prevention. Catechins have been studied for interactions with various proteins, but the mechanisms of the various catechins are not yet elucidated. Based on our previous observation that nucleic acids extracted from catechin-treated cells are colored, we studied whether catechins directly interact with nucleic acids using surface plasmon resonance assay (Biacore) and cold spray ionization-mass spectrometry. These two methods clearly showed that (-)-epigallocatechin gallate (EGCG) binds to both DNA and RNA molecules: the Biacore assay indicated that four catechins bound to DNA oligomers, and cold spray ionization-mass spectrometry analysis showed one to three EGCG molecules bound to single strand 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to double-stranded (AG-CT) oligomers of various nucleotide lengths. These results suggest that multiple binding sites of EGCG are present in DNA and RNA oligomers. Double-stranded DNA (dsDNA) oligomers were detected only as EGCG-bound forms at high temperature, whereas at low temperature both the free and bound forms were detected, suggesting that EGCG protects dsDNA oligomers from dsDNA melting to single-stranded DNA. Because both galloyl and catechol groups of EGCG are essential for DNA binding, both groups seem to hold strands of DNA via their branching structure. These findings reveal for the first time the link between catechins and polynucleotides and will intensify our understanding of the effects of catechins on DNA in terms of cancer prevention.

P-chiral o-phosphinophenol as a P/O hybrid ligand: preparation and use in Cu-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones.

[reaction: see text] (S)-2-(tert-Butylmethylphosphino)phenol and its methyl ether were synthesized from tert-butyldichlorophosphine via optically active phosphine-boranes as the intermediates. The former compound was used as a P/O hybrid ligand in the Cu-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones to achieve high enantioselectivity of up to 96%.

ent-halimane diterpenes and a guaiane sesquiterpene from Cladogynos orientalis.

Four new ent-halimane diterpenes (1-4) and one new guaiane sesquiterpene (5) were isolated from the CHCl(3) extract of the roots of Cladogynos orientalis, together with six known compounds. The structures of compounds 1-5 were established using spectroscopic methods, and the stereochemistry of chettaphanin I (6) was confirmed by X-ray crystallography.

Ten new Lycopodium alkaloids having the lycopodane skeleton isolated from Lycopodium serratum Thunb.

Ten new alkaloids, lycoposerramines-F (1), -G (2), -H (3), -I (4), -J (5), -K (6), -L (7), -M (8), -N (9), and -O (10), having lycopodine-related structures, were isolated from the club moss Lycopodium serratum THUNB. and their structures were elucidated on the basis of spectroscopic analysis and/or chemical transformation.

Structure reinvestigation of gelsemoxonine, a constituent of Gelsemium elegans, reveals a novel, azetidine-containing indole alkaloid.

[structure: see text] The structure of gelsemoxonine, isolated from Gelsemium elegans Benth., was revised to be a novel oxindole alkaloid having an azetidine unit. A new alkaloid, 14,15-dihydroxygelsenicine, which was presumed to be a biosynthetic precursor of gelsemoxonine, was also isolated.